A compound having a heavy hydrogen (deuterium and tritium) is said to be useful in various purposes. For example, a deuterated compound is very useful in clarification of reaction mechanism and substance metabolism and used widely as a labeled compound. Said compound is also known to be useful as drugs, pesticides, organic EL materials, and the like due to change in stability and property itself by isotope effect thereof. A compound having tritium also is said to be useful as a labeled compound in animal tests and the like to survey absorption, distribution, concentration in blood, secretion, metabolism and the like of drugs, etc. Therefore, research on a compound having a heavy hydrogen (deuterium and tritium) has been increasing also in these fields.
Various methods for obtaining these compounds having a heavy hydrogen have conventionally been used, however, there are many problems to be solved in deuteration technology of an aromatic ring, among others, and it was difficult to efficiently and industrially obtain a compound having a deuterated aromatic ring.
Conventional technology includes a method for deuteration of an aromatic compound under high temperature condition using heavy water and hydrochloric acid (Can. J. Chem. 1974, 52, 2169, etc.), a method for deuteration of an aromatic compound under basic condition using supercritical D2O (Tetrahedron Letters 1996, 37, 3445, etc.), a method for deuteration of an aromatic compound having a hydrophilic group under basic condition using a catalyst (JP-A-62-56441, etc.), a method for deuteration of an aromatic compound at high temperature using a non-activated catalyst (JP-A-63-198638, etc.), a method for deuteration of an organic compound under basic condition using heavy hydrogen peroxide (U.S. Pat. No. 3,849,458, etc.), a method for deuteration of a halogen atom once introduced to an aromatic compound (JP-A-6-228014, etc.), etc.
However, a deuteration method containing the addition process of an acid or a base to a reaction system is not only impossible to deuterate an aromatic compound labile to decomposition under acidic or basic condition but also has a problem that a substrate to be deuterated is limited to only an aromatic compound having a hydrophilic functional group.
Further, a modified method using heavy hydrogen peroxide, which was developed to provide deuteration of an aromatic compound having no hydrophilic functional group, cannot deuterate a compound labile to decomposition by heavy hydrogen peroxide, and further said method cannot deuterate an aromatic compound labile to decomposition by alkaline substance, which is essential to be added to a reaction system.
Furthermore, in a conventional deuteration method carried out under acidic or basic condition, complicated purification processes are required in isolation of thus deuterated compound, because reaction solution is not neutral, even if a compound not labile to decomposition under acidic or basic condition is used as a substrate.
Further, a method for deuteration under high temperature condition is difficult to be applied to a compound labile to decomposition at high temperature and a method for using supercritical D2O has a problem that a compound to be a reaction substrate tends to be decomposed due to significantly high reactivity of supercritical D2O.
Furthermore, a method for halogenation once not only requires a halogenation process of a compound to be a substrate but also has a serious problem that deuteration proceeds only at moiety introduced with a halogen atom and not at an aromatic ring itself.
In view of the above situation, development of a method is needed for deuteration of an, aromatic compound efficiently and industrially irrespective of presence and non-presence of a substituent or types thereof.